The intake of food and its conversion in the body is an essential part of life for all living creatures. Therefore, deviations in the intake and conversion of food generally lead to problems and also illness. The changes in the lifestyle and nutrition of humans, particularly in industrialised countries, have promoted obesity in recent decades. In affected people, obesity leads directly to restricted mobility and a reduction in the quality of life. There is the additional factor that obesity often leads to other diseases such as, for example, diabetes, dyslipidaemia, high blood pressure, arteriosclerosis and coronary heart disease. Moreover, high body weight alone puts an increased strain on the support and mobility apparatus, which can lead to chronic pain and diseases such as arthritis or osteoarthritis. Thus, obesity is a serious health problem for society.
The term obesity means an excess of adipose tissue. In this connection, obesity is fundamentally to be seen as the increased level of fatness which leads to a health risk. In the last analysis it is not precisely possible to draw a distinction between normal individuals and those suffering from obesity, but the health risk accompanying obesity is presumed to rise continuously as the level of fatness increases. For simplicity's sake, in the present invention, individuals with a Body Mass Index (BMI), which is defined as the body weight measured in kilograms divided by the height (in meters) squared, above a value of 25 and more particularly above 30 are preferably regarded as suffering from obesity.
Apart from physical activity and a change in nutrition, there is currently no convincing treatment option for effectively reducing body weight. However, as obesity is a major risk factor in the development of serious and even life-threatening diseases, it is all the more important to have access to pharmaceutical active substances for the prevention and/or treatment of obesity. One approach which has been proposed very recently is the therapeutic use of MCH antagonists (cf. inter alia WO 01/21577, WO 01/82925).
Melanin-concentrating hormone (MCH) is a cyclic neuropeptide consisting of 19 amino acids. It is synthesised predominantly in the hypothalamus in mammals and from there travels to other parts of the brain by the projections of hypothalamic neurones. Its biological activity is mediated in humans through two different G-protein-coupled receptors (GPCRs) from the family of rhodopsin-related GPCRs, namely the MCH receptors 1 and 2 (MCH-1R, MCH-2R).
Investigations into the function of MCH in animal models have provided good indications for a role of the peptide in regulating the energy balance, i.e. changing metabolic activity and food intake [1,2]. For example, after intraventricular administration of MCH in rats, food intake was increased compared with control animals. Additionally, transgenic rats which produce more MCH than control animals, when given a high-fat diet, responded by gaining significantly more weight than animals without an experimentally altered MCH level. It was also found that there is a positive correlation between phases of increased desire for food and the quantity of MCH mRNA in the hypothalamus of rats. However, experiments with MCH knock-out mice are particularly important in showing the function of MCH. Loss of the neuropeptide results in lean animals with a reduced fat mass, which take in significantly less food than control animals.
The anorectic effects of MCH are mediated in rodents through the G∀s-coupled MCH-1R [3-6]. Unlike primates, ferrets and dogs, no second receptor has hitherto been found in rodents. After losing the MCH-1R, knock-out mice have a lower fat mass, an increased energy conversion and, when fed on a high fat diet, do not put on weight, compared with control animals. Another indication of the importance of the MCH-MCH-1R system in regulating the energy balance results from experiments with a receptor antagonist (SNAP-7941) [3]. In long term trials the animals treated with the antagonist lose significant amounts of weight.
In addition to its anorectic effect, the MCH-1R antagonist SNAP-7941 also achieves additional anxiolytic and antidepressant effects in behavioural experiments on rats [3]. Thus, there are clear indications that the MCH-MCH-1R system is involved not only in regulating the energy balance but also in affectivity.
Literature:
    1. Qu, D., et al., A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature, 1996. 380(6571): p. 243-7.    2. Shimada, M., et al., Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature, 1998. 396(6712): p. 670-4.    3. Borowsky, B., et al., Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med, 2002. 8(8): p. 825-30.    4. Chen, Y., et al., Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology, 2002. 143(7): p. 2469-77.    5. Marsh, D. J., et al., Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci USA, 2002. 99(5): p. 3240-5.    6. Takekawa, S., et al., T-226296: A novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur J Pharmacol, 2002. 438(3): p. 129-35.
In the patent literature certain amine compounds are proposed as MCH antagonists. Thus, WO 01/21577 (Takeda) describes compounds of formula
wherein Ar1 denotes a cyclic group, X denotes a spacer, Y denotes a bond or a spacer, Ar denotes an aromatic ring which may be fused with a non-aromatic ring, R1 and R2 independently of one another denote H or a hydrocarbon group, while R1 and R2 together with the adjacent N atom may form an N-containing hetero ring and R2 with Ar may also form a spirocyclic ring, R together with the adjacent N atom and Y may form an N-containing hetero ring, as MCH antagonists for the treatment of obesity.
Moreover WO 01/82925 (Takeda) also describes compounds of formula
wherein Ar1 denotes a cyclic group, X and Y represent spacer groups, Ar denotes an optionally substituted fused polycyclic aromatic ring, R1 and R2 independently of one another represent H or a hydrocarbon group, while R1 and R2 together with the adjacent N atom may form an N-containing heterocyclic ring and R2 together with the adjacent N atom and Y may form an N-containing hetero ring, as MCH antagonists for the treatment of obesity, inter alia.Aim of the Invention
The aim of the present invention is to discover new alkyne compounds, particularly those which have an activity as MCH antagonists.
A further aim of the invention is to provide new alkyne compounds which make it possible to influence the eating behaviour of mammals and in particular achieve a reduction in body weight and/or prevent an increase in body weight in mammals.
The present invention further sets out to provide new pharmaceutical compositions which are suitable for the prevention and/or treatment of symptoms and/or diseases caused by MCH or otherwise causally connected to MCH. In particular, the aim of this invention is to provide pharmaceutical compositions for the treatment of metabolic disorders such as obesity and/or diabetes as well as diseases and/or disorders which are associated with obesity and diabetes. Other objectives of the present invention are concerned with demonstrating advantageous uses of the compounds according to the invention. The invention also sets out to provide a process for preparing the alkyne compounds according to the invention. Other aims of the present invention will be immediately apparent to the skilled man from the foregoing remarks and those that follow.
Subject Matter of the Invention
A first object of the present invention comprises alkyne compounds of general formula I
wherein                R1, R2 independently of one another denote H, a C1-8-alkyl or C3-7-cycloalkyl group optionally substituted by the group R11, while a —CH2— group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyl group may be replaced by —O—, —S— or —NR13—, or a phenyl or pyridinyl group optionally mono- or polysubstituted by the group R12 and/or monosubstituted by nitro, or                    R1 and R2 form a C2-8-alkylene bridge wherein                            one or two —CH2— groups may be replaced independently of one another by —O—, —S—, —SO—, —(SO2)—, —C═N—R18—, —C═N—O—R18—, —CO—, —C(═CH2)— or —NR13— in such a way that heteroatoms are not directly connected to one another,                                    while in the above-defined alkylene bridge one or more H atoms may be replaced by R14, and            while the above-defined alkylene bridge may be substituted by one or two identical or different carbo- or heterocyclic groups Cy in such a way that the bond between the alkylene bridge and the group Cy is formed            via a single or double bond,            via a common C atom forming a spirocyclic ring system,            via two common, adjacent C and/or N atoms forming a fused bicyclic ring system or            via three or more C and/or N atoms forming a bridged ring system,                        X denotes a single bond or a C1-6-alkylene bridge wherein                    a —CH2— group may be replaced by —CH═CH— or —C≡C— and/or            one or two —CH2— groups may be replaced independently of one another by —O—, —S—, —(SO)—, —(SO2)—, —CO— or —NR4— in such a way that in each case two O, S or N atoms or an O and an S atom are not directly connected to one another,            while the bridge X may be attached to R1 including the N atom attached to R1 and X forming a heterocyclic group, while the bridge X may additionally also be attached to R2, including the N-atom attached to R2 and X, forming a heterocyclic group, and            two C atoms or one C and one N atom of the alkylene bridge may be joined together by an additional C1-4-alkylene bridge, and            a C atom may be substituted by R10 and/or one or two C atoms in each case may be substituted with one or two identical or different substituents selected from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C4-7-cycloalkenyl and C4-7-cycloalkenyl-C1-3-alkyl, while two alkyl and/or alkenyl substituents may be joined together, forming a carbocyclic ring system,            and                        W, Z independently of one another denote a single bond or a C1-4-alkylene bridge,                    while in the group W and/or Z a —CH2— group not adjacent to the —C≡C— group may be replaced by —O— or —NR5—, and            two adjacent C atoms or one C atom and an adjacent N atom may be joined together by an additional C1-4-alkylene bridge, and            in the alkylene bridge and/or in the additional alkylene bridge a C atom may be substituted by R10 and/or one or two C atoms independently of one another may be substituted by one or two identical or different C1-6-alkyl groups, while two alkyl groups may be joined together, forming a carbocyclic ring, and                        Y denotes one of the meanings given for Cy,                    while R1 may be attached to Y including the group X and the N atom attached to R1 and X, forming a heterocyclic group fused to Y, and/or            X may be attached to Y forming a carbo- or heterocyclic group fused to Y, and                        A denotes one of the meanings given for Cy and        B denotes one of the meanings given for Cy or                    C1-6-alkyl, C1-6-alkenyl, C1-6-alkynyl, C3-7-cycloalkyl-C1-3-alkyl, C3-7-cycloalkenyl-C1-3-alkyl, C3-7-cycloalkyl-C1-3-alkenyl or C3-7-cycloalkyl-C1-3-alkynyl, wherein one or more C atoms may be mono- or polysubstituted by halogen and/or may be monosubstituted by hydroxy or cyano and/or cyclic groups may be mono- or polysubstituted by R20,                        Cy denotes a carbo- or heterocyclic group selected from one of the following meanings                    a saturated 3- to 7-membered carbocyclic group,            an unsaturated 4- to 7-membered carbocyclic group,            a phenyl group,            a saturated 4- to 7-membered or unsaturated 5- to 7-membered heterocyclic group with an N, O or S atom as heteroatom,            a saturated or unsaturated 5- to 7-membered heterocyclic group with two or more N atoms or with one or two N atoms and an O or S atom as heteroatoms,            an aromatic heterocyclic 5- or 6-membered group with one or more identical or different heteroatoms selected from N, O and/or S,            while the above-mentioned 4-, 5-, 6- or 7-membered groups may be attached via two common, adjacent C atoms fused to a phenyl or pyridine ring, and            in the above-mentioned 5-, 6- or 7-membered groups one or two non-adjacent —CH2— groups may be replaced independently of one another by a —CO—, —C(═CH2)—, —(SO)— or —(SO2)— group, and            the above-mentioned saturated 6- or 7-membered groups may also be present as bridged ring systems with an imino, (C1-4-alkyl)-imino, methylene, (C1-4-alkyl)-methylene or di-(C1-4-alkyl)-methylene bridge, and            the above-mentioned cyclic groups may be mono- or polysubstituted at one or more C atoms with R20, in the case of a phenyl group they may also additionally be monosubstituted with nitro, and/or one or more NH groups may be substituted with R21,                        R4, R5 independently of one another have one of the meanings given for R17,        R10 denotes hydroxy, ω-hydroxy-C1-3-alkyl, C1-4-alkoxy, ω-(C1-4-alkoxy)-C1-3-alkyl, carboxy, C1-4-alkoxycarbonyl, amino, C1-4-alkyl-amino, di-(C1-4-alkyl)-amino, cyclo-C3-6-alkyleneimino, amino-C1-3-alkyl, C1-4-alkyl-amino-C1-3-alkyl, di-(C1-4-alkyl)-amino-C1-3-alkyl, cyclo-C3-6-alkyleneimino-C1-3-alkyl, amino-C2-3-alkoxy, C1-4-alkyl-amino-C2-3-alkoxy, di-(C1-4-alkyl)-amino-C2-3-alkoxy, cyclo-C3-6-alkyleneimino-C2-3-alkoxy, aminocarbonyl, C1-4-alkyl-aminocarbonyl, di-(C1-4-alkyl)-aminocarbonyl, cyclo-C3-6-alkyleneimino-carbonyl,        R11 denotes C2-6-alkenyl, C2-6-alkynyl, R15—O, R15—O—CO, R15—CO—O, R16R17N, R18R19N—CO or Cy,        R12 has one of the meanings given for R20,        R13 has one of the meanings given for R17, with the exception of carboxy,        R14 denotes halogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, R15—O, R15—O—CO, R15—CO, R15—CO—O, R16R17N, R18R19N—CO, R15—O—C1-3-alkyl, R15—O—CO—C1-3-alkyl, R15—O—CO—NH, R15—SO2—NH, R15—O—CO—NH—C1-3-alkyl, R15—SO2—NH—C1-3-alkyl, R15—CO—C1-3-alkyl, R15—CO—O—C1-3-alkyl, R16R17N—C1-3-alkyl, R18R19N—CO—C1-3-alkyl or Cy-C1-3-alkyl,        R15 denotes H, C1-4-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, pyridinyl or pyridinyl-C1-3-alkyl,        R16 denotes H, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C4-7-cycloalkenyl, C4-7-cycloalkenyl-C1-3-alkyl, ω-hydroxy-C2-3-alkyl, ω-(C1-4-alkoxy)-C2-3-alkyl, amino-C2-6-alkyl, C1-4-alkyl-amino-C2-6-alkyl, di-(C1-4-alkyl)-amino-C2-6-alkyl or cyclo-C3-6-alkyleneimino-C2-6-alkyl,        R17 has one of the meanings given for R16 or denotes phenyl, phenyl-C1-3-alkyl, pyridinyl, dioxolan-2-yl, —CHO, C1-4-alkylcarbonyl, carboxy, hydroxycarbonyl-C1-3-alkyl, C1-4-alkoxycarbonyl, C1-4-alkoxycarbonyl-C1-3-alkyl, C1-4-alkylcarbonylamino-C2-3-alkyl, N—(C1-4-alkylcarbonyl)-N—(C1-4-alkyl)-amino-C2-3-alkyl, C1-4-alkylsulphonyl, C1-4-alkylsulphonylamino-C2-3-alkyl or N—(C1-4-alkylsulphonyl)-N—(C1-4-alkyl)-amino-C2-3-alkyl        R18, R19 independently of one another denote H or C1-6-alkyl,        R20 denotes halogen, hydroxy, cyano, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, hydroxy-C1-3-alkyl, R22—C1-3-alkyl or has one of the meanings given for R22,        R21 denotes C1-4-alkyl, ω-hydroxy-C2-6-alkyl, ω-C1-4-alkoxy-C2-6-alkyl, ω-C1-4-alkyl-amino-C2-6-alkyl, ω-di-(C1-4-alkyl)-amino-C2-6-alkyl, ω-cyclo-C3-6-alkyleneimino-C2-6-alkyl, phenyl, phenyl-C1-3-alkyl, C1-4-alkyl-carbonyl, C1-4-alkoxy-carbonyl, C1-4-alkylsulphonyl, phenylcarbonyl or phenyl-C1-3-alkyl-carbonyl,        R22 denotes pyridinyl, phenyl, phenyl-C1-3-alkoxy, OHC, HO—N═HC, C1-4-alkoxy-N═HC, C1-4-alkoxy, C1-4-alkylthio, carboxy, C1-4-alkylcarbonyl, C1-4-alkoxycarbonyl, aminocarbonyl, C1-4-alkylamino-carbonyl, di-(C1-4-alkyl)-aminocarbonyl, cyclo-C3-6-alkyl-amino-carbonyl, cyclo-C3-6-alkyleneimino-carbonyl, cyclo-C3-6-alkyleneimino-C2-4-alkyl-aminocarbonyl, C1-4-alkyl-sulphonyl, C1-4-alkyl-sulphinyl, C1-4-alkyl-sulphonylamino, amino, C1-4-alkylamino, di-(C1-4-alkyl)-amino, C1-4-alkyl-carbonyl-amino, cyclo-C3-6-alkyleneimino, phenyl-C1-3-alkylamino, N—(C1-4-alkyl)-phenyl-C1-3-alkylamino, acetylamino, propionylamino, phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxy-C2-3-alkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino or alkylaminocarbonylamino,while in the above-mentioned groups and residues, particularly in A, B, W, X, Y, Z, R1 to R5 and R10 to R22, in each case one or more C atoms may additionally be mono- or polysubstituted by F and/or in each case one or two C atoms independently of one another may additionally be monosubstituted by Cl or Br and/or in each case one or more phenyl rings independently of one another additionally have one, two or three substituents selected from among F, Cl, Br, I, cyano, C1-4-alkyl, C1-4-alkoxy, difluoromethyl, trifluoromethyl, hydroxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, acetylamino, aminocarbonyl, difluoromethoxy, trifluoromethoxy, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl- and di-(C1-3-alkyl)-amino-C1-3-alkyl- and/or may be monosubstituted by nitro, andthe H atom of any carboxy group present or an H atom bound to an N atom may each be replaced by a group which can be cleaved in vivo,the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.        
The invention also relates to the compounds in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates, in the form of the tautomers and in the form of the free bases or the corresponding acid addition salts with pharmacologically safe acids. The subject of the invention also includes the compounds according to the invention, including the salts thereof, wherein one or more hydrogen atoms are replaced by deuterium.
This invention also includes the physiologically acceptable salts of the alkyne compounds according to the invention as described above and hereinafter.
This invention also relates to compositions containing at least one alkyne compound according to the invention and/or a salt according to the invention optionally together with one or more physiologically acceptable excipients.
Also covered by this invention are pharmaceutical compositions containing at least one alkyne compound according to the invention and/or a salt according to the invention optionally together with one or more inert carriers and/or diluents.
This invention also relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for influencing the eating behaviour of a mammal.
The invention further relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for reducing the body weight and/or for preventing an increase in the body weight of a mammal.
The invention also relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition with an MCH receptor-antagonistic activity, particularly with an MCH-1 receptor-antagonistic activity.
This invention also relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition which is suitable for the prevention and/or treatment of symptoms and/or diseases which are caused by MCH or are otherwise causally connected with MCH.
A further object of this invention is the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition which is suitable for the prevention and/or treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, bulimia nervosa, cachexia, anorexia, anorexia nervosa and hyperphagia
The invention also relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition which is suitable for the prevention and/or treatment of diseases and/or disorders associated with obesity, particularly diabetes, especially type II diabetes, complications of diabetes including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, insulin resistance, pathological glucose tolerance, encephalorrhagia, cardiac insufficiency, cardiovascular diseases, particularly arteriosclerosis and high blood pressure, arthritis and gonitis.
In addition the present invention relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition which is suitable for the prevention and/or treatment of hyperlipidaemia, cellulitis, fat accumulation, malignant mastocytosis, systemic mastocytosis, emotional disorders, affective disorders, depression, anxiety, sleep disorders, reproductive disorders, sexual disorders, memory disorders, epilepsy, forms of dementia and hormonal disorders.
The invention also relates to the use of at least one alkyne compound according to the invention and/or a salt according to the invention for preparing a pharmaceutical composition which is suitable for the prevention and/or treatment of urinary problems, such as for example urinary incontinence, overactive bladder, urgency, nycturia and enuresis.
The invention further relates to processes for preparing for preparing a pharmaceutical composition according to the invention, characterised in that at least one alkyne compound according to the invention and/or a salt according to the invention is incorporated in one or more inert carriers and/or diluents by a non-chemical method.
The invention also relates to a pharmaceutical composition containing a first active substance which is selected from the alkyne compounds according to the invention and/or the corresponding salts as well as a second active substance which is selected from the group consisting of active substances for the treatment of diabetes, active substances for the treatment of diabetic complications, active substances for the treatment of obesity, preferably other than MCH antagonists, active substances for the treatment of high blood pressure, active substances for the treatment of hyperlipidaemia, including arteriosclerosis, active substances for the treatment of arthritis, active substances for the treatment of anxiety states and active substances for the treatment of depression, optionally together with one or more inert carriers and/or diluents.
This invention further relates to a process for preparing alkyne compounds of formula A.5R1R2N—X—Y—C≡C—W-A-B  (A.5)while in formulae A.1, A.2, A.3, A.4 and A.5 R1, R2, X, Y, W, A and B have one of the meanings given hereinbefore and hereinafter and Y denotes aryl or heteroaryl,wherein a halogen compound of formula A.1HO—X—Y-Hal  (A.1)wherein Hal denotes chlorine, bromine or iodine, preferably bromine or iodine,is reacted with an alkyne compound of formula A.2H—C≡C—W-A-B  (A.2)in the presence of a suitable palladium catalyst, a suitable base and copper(I)iodide in a suitable solvent, andthe resulting compound of formula A.3HO—X—Y—C≡C—W-A-B  (A.3)is reacted with methanesulphonic acid chloride (MsCl) to form the methanesulphonate derivative A.4,MsO—X—Y—C≡C—W-A-B  (A.4)which is further reacted with an amine of formula H—NR1R2 to obtain the end product A.5.
This invention further relates to a process for preparing alkyne compounds of formula B.5R1R2N—X—Y-Z-C≡C-A-B  (B.5)while in formulae B.1, B.2, B.3, B.4 and B.5 R1, R2, X, Y, Z, A and B have one of the meanings given hereinbefore and hereinafter and A particularly denotes aryl or heteroaryl,wherein a halogen compound of formula B.1Hal-A-B  (B.1)wherein Hal denotes chlorine, bromine or iodine, preferably bromine or iodine,is reacted with an alkyne compound of formula B.2HO—X—Y-Z-C≡C—H  (B.2)in the presence of a suitable palladium catalyst, a suitable base and copper(I)iodide in a suitable solvent, andthe resulting compound of formula B.3HO—X—Y-Z-C≡C-A-B  (B.3)is reacted with methanesulphonic acid chloride (MsCl) to form the methanesulphonate derivative B.4,MsO—X—Y-Z-C≡C-A-B  (B.4)which is further reacted with an amine of formula H—NR1R2 to obtain the end product B.5.
Moreover this invention relates to a process for preparing alkyne compounds of formula C.3R1R2N—X—Y—C≡C—W-A-B  (C.3)while in formulae C.1, C.2 and C.3 R1, R2, X, Y, W, A and B have one of the meanings given hereinbefore and hereinafter and Y denotes aryl or heteroaryl,wherein a halogen compound of formula C.1R1R2N—X—Y-Hal  (C.1)wherein Hal denotes chlorine, bromine or iodine, preferably bromine or iodine,is further reacted with an alkyne compound of formula C.2H—C≡C—W-A-B  (C.2)in the presence of a suitable palladium catalyst, a suitable base and copper(I)iodide in a suitable solvent to obtain the end product C.3.
This invention further relates to a process for preparing alkyne compounds of formula D.3R1R2N—X—Y-Z-C≡C-A-B  (D.3)while in formulae D.1, D.2 and D.3 R1, R2, X, Y, Z, A and B have one of the meanings given hereinbefore and hereinafter and A particularly denotes aryl or heteroaryl,wherein a halogen compound of formula D.2Hal-A-B  (D.2)wherein Hal denotes chlorine, bromine or iodine, preferably bromine or iodine, is reacted with an alkyne compound of formula D.1R1R2N—X—Y-Z-C≡C—H  (D.1)in the presence of a suitable palladium catalyst, a suitable base and copper(I)iodide in a suitable solvent to obtain the end product D.3.